Expression of Glial Cell Line-derived Neurotrophic Factor and Its Receptors in Glioblastoma.

IF 1.5 4区 生物学 Q4 CELL BIOLOGY
Jesper Dupont Ewald, Arnon Møldrup Knudsen, Helle Wohlleben, Lone Christiansen, Signe Regner Michaelsen, Atul Anand, Bjarne Winther Kristensen
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引用次数: 0

Abstract

Glioblastoma is the most frequent and aggressive primary brain cancer in adults, and the prognosis is poor. The neurotrophic factor glial cell-derived neurotrophic factor (GDNF) and its receptors, which are involved in neuronal development, have in experimental studies been suggested to drive tumorigenic processes in glioblastoma, but the role and expression in glioblastoma in patients is under-investigated. The aim of this study was to investigate the expression of GDNF, GDNF family receptor 1-4 (GFRA1-4), and the downstream REarranged during Transfection (RET) receptor in human glioblastoma tissue by RNA in situ hybridization, immunohistochemistry, and immunofluorescence. Expression was quantified by software-based classifiers. The results showed that GDNF was expressed in approximately 10% of tumor cells. The GFRA1 receptor was widely expressed in tumor cells, often colocalizing with the astrocytic tumor cell marker glial fibrillary acidic protein (GFAP), and in a smaller fraction of tumor cells expressing the stem cell markers oligodendrocyte transcription factor 2 (OLIG2) and SRY-Box Transcription Factor 2 (SOX2). The GFRA2 receptor expression was very limited, whereas expression of GFRA3, GFRA4, and RET, respectively, was almost absent. In conclusion, GDNF and its primary receptor GFRA1 were expressed in patient glioblastoma tissue. Potential clinical value needs further investigation.

胶质细胞源性神经营养因子及其受体在胶质母细胞瘤中的表达。
胶质母细胞瘤是成人最常见、最具侵袭性的原发性脑癌,预后较差。神经营养因子胶质细胞源性神经营养因子(GDNF)及其受体,参与神经元的发育,在实验研究中被认为是驱动胶质母细胞瘤的致瘤过程,但在胶质母细胞瘤患者中的作用和表达尚不清楚。本研究旨在通过RNA原位杂交、免疫组织化学和免疫荧光技术研究GDNF、GDNF家族受体1-4 (GFRA1-4)及其下游转染过程重排(RET)受体在人胶质母细胞瘤组织中的表达。通过基于软件的分类器对表达进行量化。结果显示,GDNF在约10%的肿瘤细胞中表达。GFRA1受体在肿瘤细胞中广泛表达,通常与星形细胞肿瘤细胞标记物胶质纤维酸性蛋白(GFAP)共定位,在较小比例的肿瘤细胞中表达干细胞标记物少突胶质细胞转录因子2 (OLIG2)和SRY-Box转录因子2 (SOX2)。GFRA2受体表达非常有限,而GFRA3、GFRA4和RET几乎不表达。综上所述,GDNF及其主要受体GFRA1在胶质母细胞瘤患者组织中表达。潜在的临床价值有待进一步研究。
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来源期刊
CiteScore
6.00
自引率
0.00%
发文量
32
审稿时长
1 months
期刊介绍: Journal of Histochemistry & Cytochemistry (JHC) has been a pre-eminent cell biology journal for over 50 years. Published monthly, JHC offers primary research articles, timely reviews, editorials, and perspectives on the structure and function of cells, tissues, and organs, as well as mechanisms of development, differentiation, and disease. JHC also publishes new developments in microscopy and imaging, especially where imaging techniques complement current genetic, molecular and biochemical investigations of cell and tissue function. JHC offers generous space for articles and recognizing the value of images that reveal molecular, cellular and tissue organization, offers free color to all authors.
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